In contrast to the glucocorticoid receptor, the thyroid hormone receptor is translated in the DNA binding state and is not associated with hsp90.
We have recently reported that the glucocorticoid receptor (GR) becomes bound to the 90-kDa heat shock protein (hsp90) at or near the end of receptor translation in vitro (Dalman, F. C., Bresnick, E. H., Patel, P. D., Perdew, G. H., Watson, S. J., Jr., and Pratt, W. B. (1989) J. Biol. Chem. 264, 19815-19821). In this paper we compare the hsp90 binding and DNA binding activities of the thyroid hormone receptor (TR) to those of the GR after cell-free translation of the two receptors in rabbit reticulocyte lysate. In contrast to the newly translated GR, which is bound to hsp90 and must be transformed to the DNA binding state, the TR is not bound to hsp90 and is translated in its DNA binding form without any requirement for transformation. When the GR is translated in wheat germ extract, which does not contain hsp90, it is translated in its DNA binding form in the same manner as the TR synthesized in reticulocyte lysate. These observations provide direct evidence that binding of GR to hsp90 is associated with repression of its DNA binding function. The fact that the TR does not bind to hsp90 and is translated in its DNA binding form is consistent with the different behavior of this receptor with respect to classic steroid receptors in the intact cell. We propose that binding to hsp90 may account for the fact that most of the steroid receptors are recovered in the cytosolic fraction after lysis of hormone-free cells in low salt buffer whereas the hormone-free TR is recovered in tight association with the nucleus.
Dalman
F C
FC
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Koenig
R J
RJ
Perdew
G H
GH
Massa
E
E
Pratt
W B
WB
D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D014176:Protein Biosynthesis; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism; D014158:Transcription, Genetic; D014908:Triticum / Q000378:metabolism
D004268:DNA-Binding Proteins; C033190:DNA-cellulose; D006360:Heat-Shock Proteins; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D002482:Cellulose; D004247:DNA; D008715:Methionine